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UniProtKB/Swiss-Prot O00255: Variant p.Gly286Arg

Menin
Gene: MEN1
Variant information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glycine (G) to Arginine (R) at position 286 (G286R, p.Gly286Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In MEN1; loss of interaction with KMT2A and JUND.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  615
The length of the canonical sequence.

Location on the sequence:   QKLLWLLYDLGHLERYPMAL  G NLADLEELEPTPGRPDPLTL
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLTL

                              QKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLTL

Mouse                         QKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLTL

Rat                           QKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLTL

Bovine                        QKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLTL

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 615 Menin
Region 219 – 395 Interaction with FANCD2
Mutagenesis 283 – 283 M -> W. Loss of interaction with KMT2A and JUND.
Mutagenesis 290 – 290 D -> R. Reduced interaction with KMT2A; when associated with R-293 and R-295.
Mutagenesis 293 – 293 E -> R. Reduced interaction with KMT2A; when associated with R-290 and R-295.
Mutagenesis 295 – 295 E -> R. Reduced interaction with KMT2A; when associated with R-290 and R-293.
Helix 282 – 294


Literature citations

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription.
Huang J.; Gurung B.; Wan B.; Matkar S.; Veniaminova N.A.; Wan K.; Merchant J.L.; Hua X.; Lei M.;
Nature 482:542-546(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-615 IN COMPLEX WITH KMT2A; PSIP1 AND JUND; INTERACTION WITH KMT2A AND JUND; INTERACTION OF KMT2A-MEN1 COMPLEX WITH PSIP1; CHARACTERIZATION OF VARIANTS MEN1 ASP-139; PHE-246; VAL-247; ARG-286 AND ARG-349; CHARACTERIZATION OF VARIANT GLN-289; MUTAGENESIS OF ALA-187; MET-283; ASP-290; GLU-293; GLU-295; TYR-324; TYR-328; GLU-371 AND ASP-375; FUNCTION;

Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein.
Wautot V.; Vercherat C.; Lespinasse J.; Chambe B.; Lenoir G.M.; Zhang C.X.; Porchet N.; Cordier M.; Beroud C.; Calender A.;
Hum. Mutat. 20:35-47(2002)
Cited for: VARIANTS MEN1 TRP-39; ASP-42; LEU-98; PRO-165; THR-165; PHE-167; ASP-169; ARG-170; TYR-177; PRO-228; PHE-245; ARG-286; PRO-316; PRO-319; TYR-322; ARG-322; ASP-342; ARG-346; HIS-362; ASP-373; MET-377; ASN-423; CYS-532; ASN-560 AND ARG-560;

Efficient mutation detection in MEN1 gene using a combination of single-strand conformation polymorphism (MDGA) and heteroduplex analysis.
Crepin M.; Escande F.; Pigny P.; Buisine M.-P.; Calender A.; Porchet N.; Odou M.-F.;
Electrophoresis 24:26-33(2003)
Cited for: VARIANTS MEN1 ARG-170; PRO-228; PHE-246; ARG-286; PRO-316; TYR-322; ASN-423 AND SER-545;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.